Diagnostic and prognostic analysis of the expression of microRNAs (miRs) expressed in material obtained by fine needle aspiration (FNAB) and peripheral blood of patients with thyroid nodules Thesis by Gustavo Bittar Cunha. Advisor: Adriano Namo Cury and Carolina Ferraz da Silva

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Introduction: The diagnosis of thyroid nodules is increasing the 80’s. Fine needle aspiration biopsy (FNAB) remains the method of choice to exclude malignancy. It is known that approximately 20-30% of FNA samples demonstrate indeterminate cytology, and only 20% of these will be diagnosed as malignant after thyroidectomy. Thus, searching for tools that could improve the accuracy of cytology, the microRNAs (miRs) emerged as possible markers. miRs act as negative regulators of oncogenes and tumor suppression genes, directly influencing the pathophysiology of malignant tumors. In this sense, the idea of using them as a diagnostic marker, and adding them to the currently existing clinical tools, we could also have more accurate information regarding the prognosis of the disease. Objective: To define a miR panel to evaluate FNAB and peripheral blood samples, able to differentiate benign from malignant nodules with high accuracy and able in predicting the prognosis of patients with differentiated thyroid carcinoma. Method: Prospective evaluation of 102 samples of FNAB and 41 of peripheral blood, through RT-qPCR techniques for expression of miR-221, -222, -146b5p, -139, -145 and -484 was performed. Subsequently, their expression was compared in relation to malignant and benign samples, and in relation to current clinical tools that are used to determine prognostic factors, such as risk of recurrence (RR), type of response (TR) and risk of death (RM) . Results: in FNA samples, miR-221, -146b-5p and -484 were significant in diagnosing malignant nodules. However, in blood samples, only miR146b-5p showed differential expression. Both, the increase in miR-222 and miR-146b-5p were related to higher RR when evaluated in FNA samples. In serum samples, only miR146b-5p correlated with higher RR. Considering the evaluation of the entire panel, the evaluation of the association of the studied miRs was shown to be 77.05% accurate in FNA samples and 79.05% in serum samples. Conclusion: With the use of the proposed panel, we could have avoided 14 of the 20 surgeries performed in the patients with indeterminate cytology, a number that represents a 70% reduction in the indication of thyroidectomies that after the procedure proved to be unnecessary. In addition, the association of miRs expression with worse prognosis, especially for miR-146b-5p, shows that this can be used as a possible marker of disease recurrence and, in some cases, assisting in risk stratification and, consequently, in defining goals. of TSH and other therapies in the follow-up of CTDs patients.

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